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May 11, 2007 

CENTER FOR VETERINARY BIOLOGICS NOTICE NO. 07-07

Subject: Post-Challenge Observation Periods for Efficacy Studies 

To: Biologics Licensees, Permittees, and Applicants 

 Directors, Center for Veterinary Biologics 

I. PURPOSE

This notice provides clarification to licensees, permittees, and applicants of current 

Center for Veterinary Biologics (CVB) policy regarding post-challenge observation 

periods in efficacy studies. This policy pertains to pivotal efficacy studies conducted to 

support product label claims, as well as routine efficacy studies intended to qualify or 

requalify potency reference preparations. 

II. BACKGROUND

Animal vaccination-challenge studies are frequently performed to demonstrate product 

efficacy. The CVB approves label claims for efficacy upon the demonstration of 

statistically significant, clinically relevant differences in post-challenge disease between 

vaccinated test animals vs. placebo-vaccinated control animals. Label claims are based 

on disease prevention or a meaningful reduction in disease severity or duration. Claims 

are not typically granted for products that merely delay disease onset or increase the time 

to peak disease severity. 

Protocols for efficacy studies should include the period of time that the animals will be 

observed for signs of disease after exposure to challenge. This period is typically based 

on the expected incubation period of the disease agent and the expected duration of 

clinical disease. Many study-specific factors, however, can impact the actual time that 

elapses from challenge-exposure to the resolution of clinical disease. In individual cases, 

the post-challenge observation period proposed in the study protocol may be insufficient 

to evaluate all of the relevant post-challenge manifestations of disease, and protocol 

deviations to increase the observation period may be justified. 

III. ACTION

Studies should be designed to have an appropriate observation period. The length of the 

observations period specified in the protocol should be the same for all subjects and 

appropriate for the disease course and study objective. 

United States 

Department of 

Agriculture

Animal and Plant 

Health Inspection 

Service 

Veterinary Services 

Center for Veterinary 

Biologics 

510 S. 17th Street, 

Suite 104 

Ames, IA 50010 

(515) 232-5785 

FAX (515) 232-7120 
Center for Veterinary Biologics Notice No. 07-07 2 

The post-challenge observation period stated in the study protocol should be considered a 

minimum interval during which all study subjects will be evaluated for relevant signs of 

disease. The presence of clinical signs of disease at the end of the planned observation 

period may indicate that the planned observation period is not long enough to properly 

assess the study objectives. The best course of action in such cases is usually to extend 

the observation period until clinical signs resolve. All reports describing studies in which 

the post-challenge observations are terminated prior to the resolution of relevant clinical 

signs and other substantive features of the disease should include a justification why 

continued observation would not have materially affected the conclusions drawn from the 

study. 

/s/Richard E. Hill, Jr. 

Richard E. Hill, Jr. 

Director 

Center for Veterinary Biologics